Immune system plays a crucial role in the physiological and pathological regulation of the cardiovascular system. The exploration history and milestones of immune system in cardiovascular diseases (CVDs) have evolved from the initial discovery of chronic inflammation in atherosclerosis to large-scale clinical studies confirming the importance of anti-inflammatory therapy in treating CVDs. This progress has been facilitated by advancements in various technological approaches, including multi-omics analysis (single-cell sequencing, spatial transcriptome et al.) and significant improvements in immunotherapy techniques such as chimeric antigen receptor (CAR)-T cell therapy. Both innate and adaptive immunity holds a pivotal role in CVDs, involving Toll-like receptor (TLR) signaling pathway, nucleotide-binding oligomerization domain-containing proteins 1 and 2 (NOD1/2) signaling pathway, inflammasome signaling pathway, RNA and DNA sensing signaling pathway, as well as antibody-mediated and complement-dependent systems. Meanwhile, immune responses are simultaneously regulated by multi-level regulations in CVDs, including epigenetics (DNA, RNA, protein) and other key signaling pathways in CVDs, interactions among immune cells, and interactions between immune and cardiac or vascular cells. Remarkably, based on the progress in basic research on immune responses in the cardiovascular system, significant advancements have also been made in pre-clinical and clinical studies of immunotherapy. This review provides an overview of the role of immune system in the cardiovascular system, providing in-depth insights into the physiological and pathological regulation of immune responses in various CVDs, highlighting the impact of multi-level regulation of immune responses in CVDs. Finally, we also discuss pre-clinical and clinical strategies targeting the immune system and translational implications in CVDs.

We evaluated the association of preprocedure CHA ₂ DS ₂ -VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, and sex) score with ischemic events in patients undergoing percutaneous coronary intervention (PCI). The Dryad Digital Repository enrolled 2533 patients between July 2009 and August 2011. We recorded 1-year ischemic events. Univariate and multivariable logistic regression analyses were used to analyze the association between CHA ₂ DS ₂ -VASc score and ischemic events. Receiver operating characteristic curves were used to evaluate the accuracy of CHA ₂ DS ₂ -VASc score in predicting long-term ischemic events. Long-term death (9.5 vs 2.8%), cardiac death (2.9 vs 1.4%), and nonfatal stroke (1.9 vs 0.7%) were significantly higher in the CHA ₂ DS ₂ -VASc score ≥2 group than the CHA ₂ DS ₂ -VASc score ≤1 group. The CHA ₂ DS ₂ -VASc score was a predictor for all-cause death (odds ratio [95% confidence interval]: 3.71 [1.89-7.30]). The risk factors for all-cause death in CHA ₂ DS ₂ -VASc score ≥2 patients included age, diagnosis, heart failure, older myocardial infarction, diabetes, and chronic obstructive pulmonary disease, while the risk factor for CHA ₂ DS ₂ -VASc score ≤1 patients was age. In conclusion, the CHA ₂ DS ₂ -VASc score is associated with long-term all-cause death, cardiac death, and stroke in patients undergoing PCI, and it may have a potential use for risk stratification for patients who undergo PCI.